The mouse submandibular gland is the richest known source of epidermal growth factor (EGF) and nerve growth factor (NGF), which are synthesized in this gland only by cells of a specialized portion of the duct, known as the granular convoluted tubule (GCT). Secretion of these factors by GCT cells is stimulated by alpha adrenergic agonists. Androgens and thyroid hormones cause hypertrophy of GCT cells, and induce the synthesis of high levels of NGF and EGF. We have recently reported a marked structural decline in the GCT compartment of C57Bl/6 male mice of advanced age, accompanied by an 80% reduction in EGF concentration in the gland. We have designed a stereologic model to determine the total number of GCT cells per gland, as well as the volume of the average mononuclear GCT (MGCT) cell. When these data are correlated with the total glandular content of either growth factor (GF) determined by radioimmunoassay, the amount of GF per MGCT cell can be established. By comparing these quantitative parameters of MGCT cells from mature (12 mo) and aged (28+ mo) male mice, we will test the hypothesis that the structural and compositional declines seen in GCT cells with senescence are due to intrinsic functional impairments. We will compare the ability of mature and aged MGCT cells to respond to acute stimulation by the alpha andrenergic agonist, phenylephrine, by studying the extent and rate of secretion and restitution of EGF and NGF, expressed per MGCT cell. We will also compare their hormonal responsiveness at these two ages to chronic stimulation by dihydrotestosterone and triiodothyronine, by studying the extent and rate of induction of hypertrophy of MGCT cells, and of increases of the two GFs per MGCT cell. These studies will contribute to an understanding of the physiologic role, in mature and aged individuals, of these two biologically potent polypeptides, which have pronounced and wide-spread effects on the growth and differentiation of a variety of tissues. Such information may prove helpful in explaining changes in control of growth with advancing age.